Anne K Bozack1, Andres Cardenas2, John Geldhof3, Quazi Quamruzzaman4, Mahmuder Rahman4, Golam Mostofa4, David C Christiani5, Molly L Kile6. 1. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W. 168th St., New York, NY, 10032, USA. 2. Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, 2121 Berkeley Way, Room 5302, Berkeley, CA, 94720, USA. 3. School of Social and Behavioral Health Sciences, College of Public Health and Human Sciences, Oregon State University, Waldo Hall 470, 2250 SW Jefferson Way, Corvallis, OR, 97331, USA. 4. Dhaka Community Hospital, 190 Wireless Railgate, Baro Moghbazar, Dhaka, 1217, Bangladesh. 5. Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Ave., Boston, MA, 02115, USA. 6. School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, 15 Milam Hall, Corvallis, OR, 97331, USA. Electronic address: Molly.Kile@OregonState.edu.
Abstract
BACKGROUND: Fetal epigenetic programming plays a critical role in development. DNA methyltransferase 3 alpha (DNMT3A), which is involved in de novo DNA methylation (DNAm), is a prime candidate gene as a mediator between prenatal exposures and birth outcomes. We evaluated the relationships between in utero arsenic (As) exposure, birth outcomes, and DNMT3A DNAm. METHODS: In a prospective Bangladeshi birth cohort, cord blood DNAm of three DNMT3A CpGs was measured using bisulfite pyrosequencing. Maternal toenail As concentrations at birth were measured to estimate in utero exposure. Among vaginal births (N = 413), structural equation models (SEMs) were used to evaluate relationships between DNMT3A methylation, log2 (toenail As), birth weight, and gestational age. RESULTS: In an adjusted SEM including birth weight and gestational age, maternal toenail As levels were associated with DNMT3A DNAm (B = 0.40; 95% CI: 0.15, 0.66) and gestational age (B = -0.19 weeks; 95% CI: 0.36, -0.03). DNMT3A DNAm was associated with gestational age (B = -0.10 weeks; 95% CI: 0.16, -0.04) and birth weight (B = -11.0 g; 95% CI: 21.5, 0.4). There was an indirect effect of As on gestational age mediated through DNMT3A DNAm (B = -0.04; 95% CI: 0.08, -0.01), and there were indirect effects of maternal toenail As levels on birth weight through pathways including gestational age (B = -14.4 g; 95% CI: 29.2, -1.9), DNMT3A DNAm and gestational age (B = -3.1 g; 95% CI: 6.6, -0.8), and maternal weight gain and gestational age (B = -5.1 g; 95% CI: 9.6, -1.5). The total effect of a doubling in maternal toenail As concentration is a decrease in gestational age of 2.1 days (95% CI: 0.9, 3.3) and a decrease in birth weight of 29 g (95% CI: 14, 46). CONCLUSIONS: DNMT3A plays a critical role in fetal epigenetic programming. In utero arsenic exposure was associated with greater methylation of CpGs in DNMT3A which partially mediated associations between prenatal As exposure and birth outcomes. Additional studies are needed to verify this finding.
BACKGROUND: Fetal epigenetic programming plays a critical role in development. DNA methyltransferase 3 alpha (DNMT3A), which is involved in de novo DNA methylation (DNAm), is a prime candidate gene as a mediator between prenatal exposures and birth outcomes. We evaluated the relationships between in utero arsenic (As) exposure, birth outcomes, and DNMT3A DNAm. METHODS: In a prospective Bangladeshi birth cohort, cord blood DNAm of three DNMT3ACpGs was measured using bisulfite pyrosequencing. Maternal toenail As concentrations at birth were measured to estimate in utero exposure. Among vaginal births (N = 413), structural equation models (SEMs) were used to evaluate relationships between DNMT3A methylation, log2 (toenail As), birth weight, and gestational age. RESULTS: In an adjusted SEM including birth weight and gestational age, maternal toenail As levels were associated with DNMT3A DNAm (B = 0.40; 95% CI: 0.15, 0.66) and gestational age (B = -0.19 weeks; 95% CI: 0.36, -0.03). DNMT3A DNAm was associated with gestational age (B = -0.10 weeks; 95% CI: 0.16, -0.04) and birth weight (B = -11.0 g; 95% CI: 21.5, 0.4). There was an indirect effect of As on gestational age mediated through DNMT3A DNAm (B = -0.04; 95% CI: 0.08, -0.01), and there were indirect effects of maternal toenail As levels on birth weight through pathways including gestational age (B = -14.4 g; 95% CI: 29.2, -1.9), DNMT3A DNAm and gestational age (B = -3.1 g; 95% CI: 6.6, -0.8), and maternal weight gain and gestational age (B = -5.1 g; 95% CI: 9.6, -1.5). The total effect of a doubling in maternal toenail As concentration is a decrease in gestational age of 2.1 days (95% CI: 0.9, 3.3) and a decrease in birth weight of 29 g (95% CI: 14, 46). CONCLUSIONS:DNMT3A plays a critical role in fetal epigenetic programming. In utero arsenic exposure was associated with greater methylation of CpGs in DNMT3A which partially mediated associations between prenatal As exposure and birth outcomes. Additional studies are needed to verify this finding.
Authors: Molly L Kile; E Andres Houseman; Andrea A Baccarelli; Quazi Quamruzzaman; Mahmuder Rahman; Golam Mostofa; Andres Cardenas; Robert O Wright; David C Christiani Journal: Epigenetics Date: 2014-02-13 Impact factor: 4.528
Authors: Saara Marttila; Laura Kananen; Sergei Häyrynen; Juulia Jylhävä; Tapio Nevalainen; Antti Hervonen; Marja Jylhä; Matti Nykter; Mikko Hurme Journal: BMC Genomics Date: 2015-03-14 Impact factor: 3.969
Authors: Daniel Desaulniers; Paule Vasseur; Abigail Jacobs; M Cecilia Aguila; Norman Ertych; Miriam N Jacobs Journal: Int J Mol Sci Date: 2021-10-11 Impact factor: 5.923